This proposed 5-year development period will be used for research and training activities that will give Dr. Steven Y. Hong the skills to become an independent investigator. Dr. Hong's long-term career goals are: 1) to become an independent researcher with a faculty position at Tufts University School of Medicine conducting HIV clinical and translational research in resource-limited settings; and 2) to explore optimization of care of HIV-infected patients in resource-limited settings with a special emphasis on improving the delivery of antiretroviral therapy (ART). His short-term goal is to develop a sustainable model of tracing ART patients who have become lost from care that can be applied in resource-limited settings to minimize the emergence of HIV drug resistance and optimize patient outcomes. This training will include formal class study, a research project, and research mentorship from experts in international HIV clinical research, ART program optimization, epidemiology, biostatistics, geographic information systems (GIS), and health systems research. The training will focus on: 1) specialized epidemiologic methods; 2) data management and statistical analysis; and 3) GIS technology. The Division of Geographic Medicine and Infectious Diseases at Tufts Medical Center and the Tufts Clinical and Translational Science Institute are well known for their strong commitment to biomedical research and career development of early-stage investigators. Along with the GIS Center at Tufts University, this institution is an ideal environment for the proposed training activities. The candidate has assembled a team of outstanding mentors with varied and relevant expertise to provide guidance in his career development: Dr. Christine Wanke in international HIV clinical research, Dr. Michael Jordan in ART program optimization in resource-limited settings, Dr. Norma Terrin in biostatistics, Patrick Florance in GIS, and Dr. Philip Odonkor in health systems research. The clinical research will take place in Namibia, in collaboration with the University of Namibia Medical School and the Namibia Ministry of Health and Social Services. Loss to follow-up (LTFU) is currently one of the largest impediments to achieving ART treatment success in resource-limited settings where an average of 21% of patients are classified as LTFU in the first six months after starting ART, and up to 25% at 12 months. As such, interventions to reduce attrition from ART programs are of the utmost importance. Defaulter tracing is a common method utilized in these settings to contact and link patients who have interrupted care or treatment back into care and decrease LTFU. Optimizing methods for defaulter tracing may be a critically untapped minimal-resource intervention which could lead to high yield results. Intensifying defaulter tracing to daily tracin with the goal of linking patients back into care within 48 hours of a patient being without medication has the potential to reduce LTFU and significantly improve ART treatment outcomes. This project seeks to determine the efficacy of intensifying the tracing of patients on ART in Namibia who have become lost to care to daily tracing, in order to decrease LTFU rates and improve patient outcomes (population ART adherence, virologic suppression, and mortality). First, predictors of and reasons for LTFU will be identified in a pilot tracing study o 400 patients. Using these data to design and optimize the intervention, a cluster randomized controlled trial will be conducted in Namibia of 8 patient tracing intensification sites compared t 8 standard-of-care sites (3,200 total patients) in regards to the proposed outcomes. The Specific Aims of the project are as follows: (1) To identify predictors of and reasons for LTFU; (2) To determine the efficacy of patient tracing intensification in decreasing rates of LTFU (primary outcome), compared to standard- of-care defaulter tracing; and (3) To determine the efficacy of patient tracing intensification in improving clinical and virologic outcomes (secondary outcomes), compared to standard-of-care defaulter tracing. This research has the potential to identify a minimal-resource strategy that can be applied throughout Namibia and other resource-limited settings to address the challenge of patient retention, thus reducing morbidity and mortality in the millions of people on ART globally. PUBLIC HEALTH RELEVANCE: High rates of loss to follow-up (LTFU) of patients on antiretroviral therapy (ART) in resource-limited settings can lead to the emergence of HIV drug resistance, treatment failure, and death. This project will assess predictors of and reasons for LTFU and determine the efficacy of intensifying the tracing of ART patients in Namibia that have become lost to care, in order to decrease LTFU rates and improve patient outcomes. This research is relevant because it has the potential to identify a minimal-resource strategy that can be applied throughout Namibia and other resource-limited settings to decrease LTFU, thus reducing morbidity and mortality in the large number of people receiving ART in resource-limited settings.